Bottom Line:
Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels.Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity.These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.

Figure 8: COX2 and IL-1β response in RAW264.7 cells treated with GTA+ve and GTA-ve extracts. RAW264.7 cells were pre-treated for 4 hours with GTA+ve or GTA-ve extracts followed by the addition of LPS (1 ug/ml) for 20 hours. (A) COX2 and (B) IL-1β mRNA levels were determined by real-time rtPCR. (C) IL-1β levels following 80 ug/ml treatment in cell lysates as determined by ELISA. Asterisks indicate p < 0.05 relative to LPS treatment alone. Data are expressed as the average of three duplicate experiments ± 1S.D.

Mentions:
Similar effects were observed with TNFα upon treatment with GTA+ve extract, which showed significantly reduced mRNA transcript levels (p < 0.05, Figure 7A) as well as protein levels in cell lysates and conditioned media (Figures 7B and 7C, respectively). Consistent with the above findings, transcript levels of COX2 and IL-1β (Figures 8A and 8B), as well as IL-1β protein levels (Figure 8C), were also significantly reduced (p < 0.05) with GTA+ve treatment. The results indicate that human blood extracts containing GTAs have anti-proliferative and anti-inflammatory properties that GTA-ve extracts lack.

Bottom Line:
Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels.Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity.These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.